Project Summary Patients with severe, refractory asthma constitute approximately 5% of all asthma patients but are responsible for over 50% of all asthma-related healthcare costs. Biologic treatments for asthma, drugs which target specific etiological pathways in particular asthma cases, have begun to emerge in the market as the first individualized treatments for severe asthma. Cost of these biologics currently ranges from $10-$40k per year and does not always improve asthma symptoms in some patients. The clinical decision to keep a patient on a particular biologic is based on exacerbation count and asthma questionnaire responses at 12 weeks following treatment initiation, by which time the patient has had 3 doses (at 0 weeks, 4 weeks, and 8 weeks). Exacerbation count and patient responses to questionnaires were the primary endpoints of the clinical trials which resulted in approval and are the primary biomarkers used in clinical evaluation of response, but patient- specific biomarkers of lung function would be most beneficial for evaluation of response to these patient- specific drugs. The lack of biomarkers which can predict response to biologic treatment is an unmet clinical need. This study will address this unmet need by evaluating the potential of hyperpolarized 129Xe MRI (HPG) to detect and predict biologic response in individual patients. Hyperpolarization is the process by which the nuclear magnetism of 129Xe is greatly enhanced allowing it to be directly imaged by MRI. Subjects inhale the xenon gas, and MRI are collected yielding high-resolution maps of regional lung ventilation. The overarching hypothesis is that HPG MR can be performed in a routine clinical setting and will predict which patients respond to treatment with mepolizumab, an anti-IL-5 biologic, 8 to 12 weeks sooner than standard clinical assessment. HPG MRI will be performed in asthma patients slated to receive treatment by mepolizumab at baseline, 4-week, and 12-week time points in order to assess its potential to assess, detect, and predict patient response to mepolizumab. This may dramatically reduce costs and improve outcomes for these patients.